Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study

J Clin Oncol. 2000 Sep;18(17):3068-77. doi: 10.1200/JCO.2000.18.17.3068.

Abstract

Purpose: Gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were compared in patients with locally advanced or metastatic transitional-cell carcinoma (TCC) of the urothelium.

Patients and methods: Patients with stage IV TCC and no prior systemic chemotherapy were randomized to GC (gemcitabine 1,000 mg/m2 days 1, 8 and 15; cisplatin 70 mg/m2 day 2) or standard MVAC every 28 days for a maximum of six cycles.

Results: Four hundred five patients were randomized (GC, n = 203; MVAC, n = 202). The groups were well-balanced with respect to prognostic factors. Overall survival was similar on both arms (hazards ratio [HR], 1.04; 95% confidence interval [CI], 0.82 to 1.32; P = .75), as were time to progressive disease (HR, 1.05; 95% CI, 0.85 to 1.30), time to treatment failure (HR, 0.89; 95% CI 0.72 to 1.10), and response rate (GC, 49%; MVAC, 46%). More GC patients completed six cycles of therapy, with fewer dose adjustments. The toxic death rate was 1% on the GC arm and 3% on the MVAC arm. More GC than MVAC patients had grade 3/4 anemia (27% v 18%, respectively), and thrombocytopenia (57% v 21%, respectively). On both arms, the RBC transfusion rate was 13 of 100 cycles and grade 3/4 hemorrhage or hematuria was 2%; the platelet transfusion rate was four patients per 100 cycles and two patients per 100 cycles on GC and MVAC, respectively. More MVAC patients, compared with GC patients, had grade 3/4 neutropenia (82% v 71%, respectively), neutropenic fever (14% v 2%, respectively), neutropenic sepsis (12% v 1%, respectively), and grade 3/4 mucositis (22% v 1%, respectively) and alopecia (55% v 11%, respectively). Quality of life was maintained during treatment on both arms; however, more patients on GC fared better regarding weight, performance status, and fatigue.

Conclusion: GC provides a similar survival advantage to MVAC with a better safety profile and tolerability. This better-risk benefit ratio should change the standard of care for patients with locally advanced and metastatic TCC from MVAC to GC.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Transitional Cell / drug therapy*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Female
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Hospitalization
  • Humans
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Quality of Life
  • Survival Analysis
  • Urinary Bladder Neoplasms / drug therapy*
  • Vinblastine / administration & dosage
  • Vinblastine / adverse effects

Substances

  • Anti-Infective Agents
  • Deoxycytidine
  • Granulocyte Colony-Stimulating Factor
  • Vinblastine
  • Doxorubicin
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • gemcitabine
  • Cisplatin
  • Methotrexate

Supplementary concepts

  • M-VAC protocol